Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/12—Ketones
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
  • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom

Definitions

• the invention relates to the use of such 1,4-naphthoquinone derivatives in the specified highly diluted concentrations for immune stimulation.
• These 1,4-naphthoquinone derivatives can be used in the form of the pure, dilute chemical, as well as in the form ver thinnest vegetable extracts containing these compounds.
• Immune stimulation is understood in accordance with the publications mentioned in the context of the present application in particular as an increase in the ability of an organism to prevent unspecific infection, which can be seen in particular as an increase in phagocytosis or macrophage activity.
• This increase in phagocytosis can also be associated with stimulation of interferon production and lymphocyte stimulation, without these effects actually having to occur at the same time for immunostimulation in the sense of the present application.
• the invention can thus also be referred to as the use of 1,4-naphthoquinone derivatives, in particular the general formula given and the specifically mentioned compounds, in highly diluted form for the artificial non-specific increase in the defense against infection.
• the present invention is based on the first-time detection of immune stimulation by 1,4-naphthoquinone Derivatives of the specified type.
• the immune stimulation can be clearly demonstrated experimentally in vitro and in vivo.
• the carbon clearance test (CCT) -RES function serves as a suitable immunological test method; the granulocyte test according to Brandt, L., Scand.J. Haematol. Suppl.
• the claimed effect can thus be regarded as experimentally proven.
• the naphthoquinones were found to be effective in both oral and parenteral delivery.
• daily doses in the range from 0.5 to 10 mg / person and day, preferably in the range from 1 to 5 mg / person and day, can be calculated for the treatment of humans for oral or parenteral administration.
• Particles in the order of 20 -25 nm can only be eliminated from the organism by phagocytosis by macrophages.
• these are eliminated from the bloodstream by phagocytosis of the macrophages in the liver (Kupffer's stellate cells) and spleen.
• Plumbagin in the form of a series of diluted solutions was used in this test, and in addition to the intravenous administration described below, oral administration in appropriate body doses was also used.
• the RES activation of the test substance is checked by single or repeated administration as an aqueous solution or, in the case of water-insoluble substances, as a suspension.
• the suspension is produced in a mixture of 0.2% Tween 80, 0.2% carboxymethyl cellulose and H 2 0 by means of ultrasound (Branson Sonifier).
• the duration and strength of the sonication depend on the values used in the acute toxicity test.
• the amount of substance intended for treatment is applied either in 4 daily single doses or ip or sc once 24 hours before the start of the test.
• the highest total dose of the test substance administered is generally 30 mg / kg body weight.
• Ink suspensions with a 10% gas black content (C 11 / 1431a, Günther Wagner, Hanover) are diluted with a 1% gelatin-NaCl solution to a content of 16 mg coal / ml.
• the suspension is preheated to 37 ° C in water.
• Each mouse receives 0.2 ml / 20 g body weight administered intravenously. 3, 6, 9, 12 and 15 min. after the intravenous administration, 25 ⁇ l of blood are drawn by puncturing the orbital plexus (pipette tips, micro-selectapette, Clay Adams, Parsipanny NYUSA).
• the blood is in 2 ml of distilled water. hemolyzed.
• the coal concentration is determined photometrically (Zeiss PMQ II photometer) at a wavelength of 650 nm and a cell thickness of 1 cm. The animals are then sacrificed and liver and spleen weights are determined.
• the maximum rates of phagocytosis increase in the range from 20 to 40% were obtained in the concentration range from 10 -4 to 10 -5 mg / ml.
• a pronounced inhibition of phagocytosis was observed in the concentration range from higher concentrations of 10 -1 to 10 -2 mg / ml.
• the leukocyte-containing plasma supernatant is slowly transferred into a sterile centrifuge tube and centrifuged for 10 min at 1000 rpm in the laboratory centrifuge.
• the precipitate consists of leucocytes and residual erythrocytes.
• the precipitate is suspended in 20 ml of 0.2% saline and shaken on the Whirlimix for 20 seconds (liquid film should run along the wall of the centrifuge glass), then 20 ml of 1.6% NaCl is added and shaken (cells are now again in physiological medium). It is now centrifuged at 2000 rpm for 10 min and the supernatant is suctioned off.
• the precipitate (ND) still contains erythrocytes, so that it is necessary to repeat the hypotonic lysis twice.
• the ND is suspended with PBS without Ca 2+ / Mg 2+ and then in 2 ml PBS without Ca 2+ / Mg 2+ .
• the well-suspended cells are pipetted into a new tube and counted.
• the PMNL suspension 1:10 is diluted with Turk's solution and the existing cells are counted.
• the suspension is diluted with PBS without Ca 2+ / Mg 2+ to 1000 cells / / ul.

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• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Applications Claiming Priority (2)

Publications (1)

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ID=6243839

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Cited By (5)

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• 1984
  • 1984-08-24 DE DE19843431236 patent/DE3431236A1/de not_active Ceased
• 1985
  • 1985-08-23 EP EP19850110606 patent/EP0173262A2/fr not_active Withdrawn

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